Project Summary/Abstract Stephen Juraschek, MD, PhD, is a research fellow in the Division of General Internal Medicine at Johns Hopkins University, School of Medicine. He is applying for a Mentored Patient-Oriented Research Career Development (K23) Award, titled ?Improved characterization of postural blood pressure change in older adults.? His rigorous training and impressive body of research have prepared him for this next phase of his career. Through this award, Stephen will successfully transition from a scientist proficient in conducting secondary data analyses to an independent clinical investigator, skilled in generating primary data in trials of interventions designed to prevent and treat blood pressure-related cardiovascular disease in older adults. Stephen completed his MD-PhD training in just six years with a strong foundation in epidemiology and biostatistics. He has demonstrated great aptitude in publishing secondary analyses of completed studies focused on cardiovascular disease and hypertension. This K23 proposal, represents an opportunity for Stephen to acquire the skills that are necessary to become an independent clinical investigator. These skills include (1) a rigorous, hands-on experience in primary data collection and (2) advanced analytic techniques related to the design and conduct of clinical studies, including trials with adaptive designs. Stephen's proposal focuses on orthostatic hypotension, an incredibly important yet poorly defined side effect of antihypertensive therapy in older adults. His proposal includes a 5-year plan that leverages the infrastructure of a funded NIH trial to: (1) characterize orthostatic hypotension using a continuous feed device in 1100 participants of STURDY (cross-sectional validation study); (2) determine the association of novel metrics of orthostatic hypotension with subsequent falls (prospective cohort study); and (3) evaluate whether vitamin D lowers the prevalence of orthostatic hypotension and reduces its symptoms (response-adaptive clinical trial). Successful completion of this proposal will answer ongoing controversies surrounding the assessment and characterization of orthostatic hypotension in relation to relevant clinical outcomes as well as evaluate a novel treatment of orthostatic hypotension. Stephen's research will occur in the rich, diverse, and collaborative environment at Johns Hopkins University under the guidance and support of a dedicated group of faculty mentors, led by Dr. Lawrence Appel, MD, MPH, and Dr. Edgar Miller, MD, PhD. His mentorship team is truly multidisciplinary with faculty from the Johns Hopkins Schools of Medicine, Nursing, and Public Health. Together, this team will ensure that Stephen emerges with expertise in patient-centered, primary data collection, complex data analysis, and skills in the design and analysis of trials, including those with adaptive designs. As a result of this mentored training, Stephen will be fully equipped for a highly productive career as an independent clinical investigator focused on the prevention and treatment of blood pressure-related cardiovascular disease in older adults.